دورية أكاديمية

Functional genetic screen identifies ITPR3/calcium/RELB axis as a driver of colorectal cancer metastatic liver colonization.

التفاصيل البيبلوغرافية
العنوان: Functional genetic screen identifies ITPR3/calcium/RELB axis as a driver of colorectal cancer metastatic liver colonization.
المؤلفون: Moy RH; Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY 10065, USA., Nguyen A; Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY 10065, USA., Loo JM; Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY 10065, USA., Yamaguchi N; Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY 10065, USA., Kajba CM; Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY 10065, USA., Santhanam B; Department of Biochemistry and Molecular Biophysics and Department of Systems Biology, Columbia University, New York, NY 10032, USA; Department of Biological Sciences, Columbia University, New York, NY 10027, USA., Ostendorf BN; Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY 10065, USA., Wu YG; Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY 10065, USA., Tavazoie S; Department of Biochemistry and Molecular Biophysics and Department of Systems Biology, Columbia University, New York, NY 10032, USA; Department of Biological Sciences, Columbia University, New York, NY 10027, USA., Tavazoie SF; Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address: sohail.tavazoie@rockefeller.edu.
المصدر: Developmental cell [Dev Cell] 2022 May 09; Vol. 57 (9), pp. 1146-1159.e7. Date of Electronic Publication: 2022 Apr 28.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101120028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1551 (Electronic) Linking ISSN: 15345807 NLM ISO Abbreviation: Dev Cell Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, Mass. : Cell Press, c2001-
مواضيع طبية MeSH: Colorectal Neoplasms*/genetics , Colorectal Neoplasms*/metabolism , Liver Neoplasms*/genetics, Calcium/metabolism ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/genetics ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; NF-kappa B/metabolism ; Transcription Factor RelB/genetics ; Transcription Factor RelB/metabolism
مستخلص: Metastatic colonization is the primary cause of death from colorectal cancer (CRC). We employed genome-scale in vivo short hairpin RNA (shRNA) screening and validation to identify 26 promoters of CRC liver colonization. Among these genes, we identified a cluster that contains multiple targetable genes, including ITPR3, which promoted liver-metastatic colonization and elicited similar downstream gene expression programs. ITPR3 is a caffeine-sensitive inositol 1,4,5-triphosphate (IP3) receptor that releases calcium from the endoplasmic reticulum and enhanced metastatic colonization by inducing expression of RELB, a transcription factor that is associated with non-canonical NF-κB signaling. Genetic, cell biological, pharmacologic, and clinical association studies revealed that ITPR3 and RELB drive CRC colony formation by promoting cell survival upon substratum detachment or hypoxic exposure. RELB was sufficient to drive colonization downstream of ITPR3. Our findings implicate the ITPR3/calcium/RELB axis in CRC metastatic colony formation and uncover multiple clinico-pathologically associated targetable proteins as drivers of CRC metastatic colonization.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: T32 CA009207 United States CA NCI NIH HHS; R01 HG009065 United States HG NHGRI NIH HHS; R01 CA257153 United States CA NCI NIH HHS; T32 GM007739 United States GM NIGMS NIH HHS; K08 CA263304 United States CA NCI NIH HHS; U54 CA261701 United States CA NCI NIH HHS; United States HHMI Howard Hughes Medical Institute; UL1 TR001866 United States TR NCATS NIH HHS
فهرسة مساهمة: Keywords: ITPR3; RELB; calcium; colorectal cancer; hypoxia; metastasis; non-canonical NF-κB
المشرفين على المادة: 0 (ITPR3 protein, human)
0 (Inositol 1,4,5-Trisphosphate Receptors)
0 (NF-kappa B)
0 (RELB protein, human)
147337-75-5 (Transcription Factor RelB)
SY7Q814VUP (Calcium)
تواريخ الأحداث: Date Created: 20220429 Date Completed: 20220512 Latest Revision: 20231202
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9446818
DOI: 10.1016/j.devcel.2022.04.010
PMID: 35487218
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-1551
DOI:10.1016/j.devcel.2022.04.010